Genetic testing for hereditary breast and ovarian cancer: responsibility and choice

Genetic testing for hereditary breast-ovarian cancer has become an important part of clinical genetics practice. Although considerable work has focused on the psychological impact of this technology, there has been little research into the moral implications of genetic information on hereditary cancer families. In this article, the author examines moral issues related to individuals' decisions to seek or decline testing. In-depth interviews with 53 participants make up the core of the research. Analysis of participants' accounts illustrates how the decision to be tested (or not) interconnects with moral agency and aspects of self (embodied, familial-relational, and civic self). The findings form the foundation for inquiry into conceptualization of moral responsibility, autonomy, and choice. They also provide insight that might assist clinicians to understand more fully the needs and responses of those who seek genetic testing for hereditary breast-ovarian cancer.     

Genetic testing for breast and ovarian cancer susceptibility: evaluating direct-to-consumer marketing--Atlanta, Denver, Raleigh-Durham, and Seattle, 2003

Breast and ovarian cancer are the second and fifth leading causes of cancer death, respectively, among women in the United States. One in eight women will have breast cancer during their lifetimes, and one in 70 will have ovarian cancer. Mutations in two genes, BRCA1 and BRCA2 (BRCA1/2), are associated with predisposition for inherited breast and ovarian cancer and are identified in 5%-10% of women with breast or ovarian cancer (BOC). Since 1996, genetic testing for these mutations has been available clinically; however, population-based screening is not recommended because of the complexity of test interpretation and limited data on clinical validity and utility. Despite the test's limited applicability in the general population, the U.S. provider of clinical BRCA1/2 testing (Myriad Genetic Laboratories, Inc., Salt Lake City, Utah) conducted a pilot direct-to-consumer (DTC) marketing campaign in two cities (Atlanta, Georgia, and Denver, Colorado) during September 2002-February 2003. Although DTC advertisements have been used to raise consumer awareness about pharmaceuticals, this was the first time an established genetic test was marketed to the public. To assess the impact of the campaign on consumer behaviors and health-care provider practices, CDC and the respective state health departments for the pilot cities and two comparison cities (Raleigh-Durham, North Carolina, and Seattle, Washington) surveyed consumers and providers. This report summarizes results of those surveys, which indicated that consumer and provider awareness of BRCA1/2 testing increased in the pilot cities and that providers in these cities perceived an impact on their practice (e.g., more questions asked about testing, more BRCA1/2 tests requested, and more tests ordered). However, in all four cities, providers often lacked knowledge to advise patients about inherited BOC and testing. These findings underscore the need for evidence-based recommendations on appropriate use of genetic tests and education of providers and the public to achieve maximum individual and public health benefit from genetic testing.     

Ethical and public health considerations in HIV counseling and testing: policy implications

HIV counseling and testing is broadly considered a critical component of HIV transmission-prevention and treatment efforts. Given the severity of the AIDS pandemic in sub-Saharan Africa, the potential societal benefit of testing is invoked to call for its massive expansion and to justify a shift from voluntary to routine testing. Surprisingly little evidence has demonstrated, however, that such a shift will result in the intended benefits to communities, particularly that of reducing the horizontal transmission of HIV. This analysis addresses and critiques the assumptions underlying a serostatus-based approach to behavior change and discusses the ethical consequences of transferring control of the decision to be tested from the individual to the provider. It concludes with a discussion of the implications for HIV counseling and testing policies and proposes alternatives to routine testing that have the potential to be effective while preserving the right to know one's HIV status.     

Secondary prevention: screening for breast cancer

Screening healthy women in order to detect the earliest signs of breast cancer may offer a possibility of curing many breast cancer patients who would be incurable if left until they developed symptoms. However, the natural history of breast cancer is very variable, probably indicating a wide spectrum of different growth rates of the tumour. Therefore it cannot necessarily be assumed that cancers detected by screening at an apparently early stage will behave in the same way as symptomatic cancers at that stage. To prove that screening enables cancer to be cured one needs to compare the number of deaths in a group of women who have been offered screening with those in a comparable group who have not. Unlike the situation in clinical trials of different treatments, comparison of the survival of screen-detected cancers with symptom-detected cancers is inadequate proof, because of selection bias, lead-time bias and length-bias. One randomized controlled trial of screening for breast cancer has so far been published and this shows that women in the group who were offered screening suffered one third fewer deaths from breast cancer than women in the control group, the difference persisting for up to 14 years from the first screening invitation. Further trials are now under way in Canada and various European countries, hoping to confirm this finding and to explore various other issues. Of the screening test methods currently available mammography seems the most sensitive and specific and its radiation hazard is now of almost negligible proportions provided that regular careful monitoring of the equipment is carried out. However it may have the disadvantage of overdiagnosing cases of borderline non-invasive neoplasia which might not progress to invasive cancer within the woman's lifetime. Clinical examination of the breasts is a less satisfactory test in older women but it may be useful in premenopausal women in whom mammography is less sensitive. The validity of self-examination of the breasts by women themselves is still largely unknown, but it is unlikely that compliance with regular breast self-examination will be as high as women's acceptance of screening. Further research is required into the optimal frequency of screening and into its cost-effectiveness.     

Ethical implications and practical considerations of ethnically targeted screening for genetic disorders: the case of hemoglobinopathy screening

The prevalence of hemoglobinopathies differs among populations due to genetic differences and due to the protective effects of the heterozygote (carrier) state against malaria. Because of the difference in genetic distribution, public health programs have weighed the ethical versus practical implications of ethnically targeted versus universal newborn, and where applicable, prenatal screening. We examine newborn and prenatal screening for hemoglobinopathies in relation to the use of 'race' and ethnicity to assess risk for genetic conditions. First, categories of race/ethnicity are social constructs, therefore, observed or self-identified broad racial/ethnic categories are correlated but not necessarily reliable indicators of geographic ancestry or genetic risk. Second, targeting based on ethnicity poses serious issues of logistics and equity for public health programs and clinical services. In the past, newborn screening for hemoglobinopathies in the United States and United Kingdom was often selective, targeted to women of certain ethnic groups or areas with large concentrations of ethnic minority groups. Presently, newborn screening for hemoglobinopathies is universal in both countries and programs emphasize that individuals of all ethnic backgrounds are at risk for carrying a hemoglobin genetic variant. Reported race/ethnicity is still used as a criterion for offering prenatal carrier testing in the United States, where it is not a public health responsibility. In the United Kingdom, prenatal screening under the National Health Service is universal in high-prevalence areas and in low-prevalence areas is targeted based on reported ancestry. The continued use of targeted prenatal screening in both countries reflects the different purposes and modes of laboratory testing in newborn and prenatal screening. The ethical imperative to identify as many affected infants with life-threatening conditions as possible in newborn screening programs is not applicable to prenatal carrier testing. Because newborn screening dried blood spot specimens are tested for multiple disorders, targeted screening poses serious logistical challenges which is not the case in prenatal screening.     

Mass screening for breast cancer

Breast cancer is now the most common cancer in women. There is a certain correlation between the stage of the disease at diagnosis and outcome after treatment. Several studies have been initiated involving mammography with or without physical examination aimed at early detection of breast cancer in asymptomatic women. In order to review the results to date, a meeting was held in Reykjavík in April 1984 organized by international and Icelandic health agencies and attended by senior investigators of the ongoing screening studies. A summary of the available data is presented in this paper along with the conclusions of the meeting.     

Generic screening for breast cancer

Following the cloning of BRCA1 and BRCA2 it has been suggested that genetic screening may be of benefit for women at high familial risk. To be able to assess whether this is the case more research is needed on the penetrance of the different mutations, their prevalence in the population, the biological and environmental factors affecting the development of cancer in mutation carriers and the natural history of genetically determined breast cancer. Furthermore, studies on the efficacy of preventive measures, on counselling and on psychological effects of testing are also needed.     

Anorexia nervosa: psychological considerations for nutrition counseling

This article presents the underlying psychological beliefs and self-perceptions held by individuals with anorexia nervosa. The intent of this article is to help dietitians and other nutrition counselors become more aware of the psychological characteristics of individuals with anorexia nervosa and become familiar with various counseling skills that can assist counselors when they are working toward reaching the goal of re-establishing normal eating patterns and attitudes about food. Counseling approaches that may be used by the nutrition counselor in an effort to deal effectively with the various psychological characteristics displayed by anorexics are provided. Nutrition counselors must be well informed of the psychodynamic aspects that prevail in the disorder, such as low self-esteem, frustration over gaining weight, and a distorted body image. In addition, nutrition counselors must be aware of the particular communication skills (e.g., attentive listening, empathic responses, and verbal encouragement) and basic therapeutic methods (e.g., encouraging self decision making and providing support and acceptance of thoughts, feelings, and actions) that can be used for effecting positive growth and changes in dietary behavior of individuals with anorexia.     

Prevention in familial breast cancer: counseling and prophylactic mastectomy

In five families with an apparent excess of breast cancer, four women elected prophylactic mastectomy to prevent breast cancer, and nine others sought counseling to explore possible means of control. Counseling addressed the women's risk factors (the largest being family history), the treatment and prognosis of the tumor, and a comparison of medical surveillance and prophylactic surgery. Personalized relative risk estimates, defined for individual factors by epidemiologic studies, were summarized as the probability of developing breast cancer within five years and ranged from 0.2% to 24%. In 1- to 12-year follow-up, none developed breast cancer. Of those counseled, the five who elected subcutaneous mastectomy with implantation and the four who chose surveillance had similar magnitude and recall of risk estimates and knowledge of control options. None of those choosing surveillance had, in fact, followed a regular program of examination. Controlling breast cancer may be possible through individualized counseling of high risk women.     

The pretentions and achievements of cancer screening,in particular breast cancer screening

The 'Vereniging Nederlands Tijdschrift voor Geneeskunde' (Dutch Journal of Medicine Association) recently held a conference about the doubts expressed in recent publications concerning the value of cancer screening and breast-cancer screening in particular. In this the discussion mainly focused on whether disease-specific mortality or overall mortality should be taken as an endpoint in the evaluation of the screening procedure. In a recent advisory report, the Health Council of the Netherlands stated that the present form of breast cancer screening ought to be continued in the Netherlands for the time being. However, during the conference it was emphasized that cancer screening must be viewed as a highly complex system. Therefore, it is impossible to measure the effects of screening by considering just one end-point, such as cancer-specific mortality. The opinion was also expressed that with the introduction of new forms of cancer screening (e.g. colon or prostate-cancer screening), experience should first of all be gained with the small-scale screening of persons with an elevated risk. This is a task in which the government should lead the way. Furthermore, the government will also need to regulate the enthusiasm that can be expected for various types of secondary preventative diagnostics offered on the free market, including cancer screening. Another important aspect of cancer screening is ensuring that the general public are thoroughly and carefully informed about the pros and cons of cancer screening. The public must know that although cancer screening can save lives, it also causes harm. People scarcely realise that screening may more often involve a loss of carefree years of life than a small chance of living longer.     

Choice of surgery for early breast cancer: psychosocial considerations

A prospective study was conducted with early breast cancer patients who had either been offered, or not been offered, a choice of surgery for treatment. The choice involved mastectomy or wide excision plus radiotherapy. Available evidence suggests that the medical outcome between these two options is similar; this study was designed to investigate selected psychosocial outcomes. It was found that whether or not patients were given a choice was of greater relevance to psychosocial outcomes that was the type of operation performed. Providing a choice led to improved reported adjustments with respect to the ability to undertake work, attitudes towards the future, beliefs about coping, and in physical and psychological functioning.     

Population screening for breast cancer: between euphoria and scepticism

Forty years after the first mammograms were made, doubts are cast on the effectiveness of population screening for breast cancer. Disease-specific and overall mortality appear to have diminished, but any real effect is small. Proponents of breast cancer screening point at the possibility of saving lives and at the obligation to do so, whereas opponents emphasise that the screening may do more harm than good and that the large funds involved might be better spent in other health care areas. If the experts cannot decide on the effectiveness, simply leaving the choice of whether or not to take part up to citizens offers no solution. These complex health care matters require complex answers, which have to be found before any population screening for cancer of prostate, colon or lung can be implemented.